Nucleotide sequences for novel protein tyrosine phosphatases

Abstract

PCT No. PCT/US94/09943 Sec. 371 Date Aug. 9, 1996 Sec. 102(e) Date Aug. 9, 1996 PCT Filed Sep. 1, 1994 PCT Pub. No. WO95/06735 PCT Pub. Date Mar. 9, 1995The invention relates to the cloning of two novel protein tyrosine phosphatases. Nucleic acid sequences encoding these phosphatases (PTPL1 and GLM-2) as well as anti-sense sequences are also provided. The recombinantly produced PTPL1 and GLM-2 proteins also are provided, as well as antibodies to these proteins. Methods relating to isolating the phosphatases, using the nucleic acid sequences, and using the phosphatases also are provided.

We claim: 
     
       1. An isolated nucleic acid molecule comprising a nucleotide sequence selected from the group consisting of (a) nucleotide sequences which hybridize under high stringency conditions to a nucleic acid molecule consiting of the nucleotide sequence of SEQ ID NO:1, and which encodes a naturally occurring PTPL1 protein tyrosine phosphatase, and   (b) nucleotide sequences that differ from the nucleotide sequences of (a) in codon sequence due to the degeneracy of the genetic code.   
     
     
       2. The isolated nucleic acid molecule of claim 1, wherein said isolated nucleic acid molecule encodes a PTPL1 comprising the amino acid sequence as set forth in SEQ ID NO:3. 
     
     
       3. The isolated nucleic acid molecule of claim 1 wherein said nucleotide sequence comprises SEQ ID NO.:1. 
     
     
       4. A method of detecting compounds which increase or decrease expression or phosphatase activity of a PTPL1 protein tyrosine phosphatase encoded by the nucleic acid molecule of claim 1 comprising the steps of (a) determining a control amount of PTPL1 protein tyrosine phosphatase expression or phosphatase activity in a cell which expresses said PTPL1 protein tyrosine phosphatase;   (b) contacting the cell which expresses said PTPL1 protein tyrosine phosphatase with a test compound;   (c) measuring the expression or phosphatase activity of said PTPL1 protein tyrosine phosphatase in said cell contacted with the test compound; and   (d) comparing the expression or phosphatase activity of said PTPL1 protein tyrosine phosphatase measured in (c) with the control amount of PTPL1 protein tyrosine phosphatase expression or phosphatase activity determined in (a) for an indication of the increase or decrease of expression or phosphatase activity of said PTPL1 protein tyrosine phosphatase.   
     
     
       5. The method of claim 4 wherein expression of said PTPL1 protein tyrosine phosphatase is measured. 
     
     
       6. The method of claim 4 wherein phosphatase activity of said PTPL1 protein tyrosine phosphatase is measured. 
     
     
       7. An isolated PTPL1 protein tyrosine phosphatase encoded by the nucleic acid molecule of claim 1 or claim 3. 
     
     
       8. An isolated nucleic acid molecule comprising a nucleic acid molecule complementary to the isolated nucleic acid molecule of claim 1. 
     
     
       9. The isolated nucleic acid molecule of any one of claims 1-3 and 8 wherein said nucleotide sequence is operably joined to a regulatory sequence. 
     
     
       10. A substantially pure protein comprising a PTPL1 protein tyrosine phosphatase wherein said PTPL1 comprises an amino acid sequence selected from the group consisting of the amino acid sequence as set forth in SEQ ID NO.:3 and a naturally occurring allelic variant of the amino acid sequence as set forth in SEQ ID NO.:3. 
     
     
       11. The substantially pure protein of claim 10 wherein said amino acid sequence comprises the amino acid sequence as forth in SEQ ID NO:3. 
     
     
       12. A method for determining whether a compound increases or decreases the phosphatase activity of a PTPL1 protein tyrosine phosphatase encoded by the nucleic acid molecule of claim 1, comprising (a) determining a control amount of phosphatase activity of the PTPL1 protein tyrosine phosphatase,   (b) contacting the PTPL1 protein tyrosine phosphatase with the compound,   (c) measuring the phosphatase activity of the PTPL1 protein tyrosine phosphatase, and   (d) comparing the phosphatase activity measured in (c) with the control amount of phosphatase activity determined in (a) as an indication whether the compound increases or decreases the phosphatase activity of the PTPL1 protein tyrosine phosphatase.